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Anaesthetized rabbits were used to examine the effects of amiloride (an inhibitor of a conductive sodium channel in the distal tubule) and atrial natriuretic peptide (ANP), both singly and in combination, on renal function and the renal kallikrein-kinin system. The administration of ANP (0.05 μg/kg per min) produced a natriuresis with increases in renal blood flow and glomerular filtration rate. The administration of ANP superimposed on amiloride infusion (5 mg/kg + 0.04 mg/kg per min) showed an additive effect on the natriuresis, although the renal haemodynamic changes were now absent. The infusion of ANP alone increased the urinary excretion of kallikrein and kinins. Prior infusion of amiloride prevented the expected increases in the urinary excretion of kallikrein and kinins after infusion of ANP was superimposed. These results suggest that the observed renal haemodynamic changes could be mediated through renal kallikrein and kinins. The additive effect on sodium excretion might be elicited by the results of alterations in the tubular handling of sodium, although distal tubular function is not modified by ANP. It seems that the renal kallikrein-kinin system is not causally involved in the increased sodium excretion by ANP.